The overall goal of the program is to elucidate the mechanisms by which the liver maintains cholesterol homeostasis. The focus of this application is to elucidate the nature and physiology of the chylomicron remnant receptor. To this end we propose to purify the receptor, characterize it and prepare an antibody to it. This antibody will be used to elucidate the relationship if any of the low density lipoprotein receptor and the chylomicron remnant receptor. Studies to examine post binding events in remnant metabolism and to quantify the roles of individual cell types in remnant metabolism are also proposed. The influence of the physical state of the environment on apo E binding will be studied. Further work to prove our hypothesis that hepatomas have a defect in remnant metabolism is planned. Lastly, we propose to explore the nature of the lipoprotein binding sites on human liver. These studies, by describing how cholesterol entry in liver is regulated, may help us to understand the pathogenesis of both atherosclerosis and cholelithiasis.